Omicron-alkyl-omicron-cycloalkyl thiophosphoric acid s-phenylesters



UnitedStates Patent O 7 The present invention relates to'and has, as itsobjects new and useful Oralkyl-O-cycloalkyl thiophosphoric acidS-phenylesters which show a remarkable activity against ectoparasites.

QO-dialkyl-phosphoric' acid-S-phenylester's are already known (cf. US.patent specification 2,861,876). These phosphorus containing compoundshave only a very low activity. against ectoparasites. The most activecompound of this group is the 0,0-diethyl-phosphoric acid- S(p-'chlorophenyl)ester .of the formula onrfio o J It has been foundthat theO-alkyl-O-cycloalkylthiophosphoric acid-S-phenylesters of the formulawherein 1 R stands for lower alkyl with 1 'to 4 carbon atoms orloweralkenyl with 1 to 4 carbon atoms,

R stands for cycloalkyl with 5 to 6 carbon atoms,.

R stands for'halogen, lower alkyl with 1 to 4 carbon atoms or loweralkoxy with l to 4 carbon atoms, and

It stands for 1 or 2,

possess a hi h activityagainst ectoparasites.

It is very surprising that the compounds according to the invention havea considerably higher activity against ectoparasites thanthe knowncompounds which are similar to the compoundsof the invention. It iscompletely surprising that the substitution of aicycloalkyl radical foralower alkyl radical increases the pesticidal activity of about 10 to250 times (of. the table below).

In the above formula ofthe compounds according to the invention -R.preferably :stands for methyLethyl and propyl. R preferably stands forcyclohexyl and cyclopentyl. R preferably stands for halogen, such aschlorine, bromine and fluorine, methyl, ethyl, methoxy and ethoxy.

The following individually mentioned compounds represent a selection ofespecially suitable compounds which can be used in accordance with theinvention:'

O-ethyl-O-cyclohexyl-thiolphosphoric-acid-S m-chloro- V phenyl)-ester,

V 0methyl-O-cyclopentyl-thiolphosphoric-acid-S(pchlorophenyl) ester,O-ethyl-O-cyclopentyl-thiolphosphoric-acid-S (p-chlorophenyl -ester,

r 3,201,444 Patented Aug. 17, 1965O-ethyl-O-cyclohexyl-thiolphosphoric-acid-S (p-chlorom-methylphenyl)-ester,

O-ethyl-O-cyclohexyl-thiolphosphoric-acid-S (p-chlorom-rnethoxyphenyl-ester.

The compounds of the invention can be produced in accordance with knownprocesses, for instance O-alkyl-O- cyclohlkyl phosphites can be reactedwith phenylsulphenic acid chlorides preferably in the presence of inertsolvent such as carbontetrachloride at temperatures between 0 and about60. Representative examples for the preparation of compounds accordingtothe invention are given below. V

The phosphorus containing compounds of the invention can be usedtocombat ectoparasites such as the several typesof ticks which'belong' tothe group of mites.

For cornbatting ectoparasites of domestic animals the spray or dipprocess is preferably used.

In the following the effectiveness of the compounds according to theinvention and their superiority over the known chemically similarcompounds is established.

The following compounds are prepared and compared:

(I, known) Aqueous dilutions of these compounds are prepared by admixing:themwith the same amount of dime-thyl formamide as an auxiliary solventadding thereto 20% by weight referred :to the active ingredient of acommercial emulsifierconsisting of a ibenzyl hydroxy polyglyeol ethercontaining about 10 to.15 glycol residues, and diluting at least thispremixture with water to the desired concentration indicated in thetable below.

The tests are carried out as follows: a) 10 femaletioks each of the typeBoophilus microplus are placed into mull bags which are brought into asolution prepared :as described above 'while moving them continuously.After 1 minute the mull bagsare taken off the active solutions and putinto glass dishes in which filter paper is placed. .The ticks are takenoff the mull bags and placed upon dry filter paper. Evaluation occurredafter 72 hours. The following results are obtained:

Concentration Compound (in percent Killing rate active ingredi- (inpercent) ent/water) The following example relates to the use of thecornpound of the invention for com'batting ticks in the skin of cattle:t n

(b) "8 young head of cattle infested by .ticks are sprayed with aqueoussuspensions prepared as indicated above containing 0.0030% of compoundsIII and IV re- 7 spectively. The living status of the ticks is evaluatedTo a solution of 45 g. (0.25 mol) of O-methyl-O-cyclohexylphosphite(boiling point 124 C./7 mm.) in 150 com. of carbon tetrachloride areadded at 20 C. with stirring 45 g. of 4-chlorophenylsulphenic acidchloride. Subsequently the reaction mixture is stirred for an hour at 20C, Subsequently the reaction mixture is washed with a solutioncontaining 3% by weight of sodium hydrogen carbonate until it reactsneutral. The organic layer is separated and dried over anhydrous sodiumsulphate and finally distilled. There are obtained 71 g. (89% of thetheory) of O-methyl-O-cyclohexyl-S-(4- c'hlorophenyl)-thiolphosphate inthe form of a water insoluble colourless oil.

Analysis.-Oaloulated for a molecular weight of 321: P, 9. 6%; S, 10.0%.Found: P, 8.1%; S, 11.0%.

Example 2 96 g. (0.5 mol) of cyclohexyl-ethyl phosphite (boiling point64 C./0.01 mm. Hg) are added with stirring to a solution of 90 g. ofp-ohlorophenyl sulphenic acid chloride in 400 com, carbon tetrachloride.Subsequently the reaction mixture is stirred for an hour at '20 C. Thereaction product is poured into 500 cc. iced water. The organic phase isseparated and dried over anhydrous sodium sulphate. The carbontetrachloride is evaponated and 142 g. of the above shown compound areobtained in a yield of 85% of the theoretical. The new ester isinsoluble in water and constitutes a colourless oil, n 1,5332.

Analysis.Calcula-ted for a molecular weight of 335: C1, 10.6%; S, 9.6%;-P, 9.3%. Found: CI, 10.2%; S, 9.8%; P, 9.3%.

The toxicity of the compound is 25 mg. per kg. rat (DL per os). In thesame way the following compounds can be obtained:

O-isopropyl-O-cyclohexyl-thiolphosphoric-acid-S (p-chlorophenyl) ester,

O-methyl-O-cyclohexyl-thiolphosphoric-acid-S(m-chlorophenyD-ester,

. a O-ethyl-O-cyclohexyl-thiolphosphoric-acid-S(tn-chloropheny1)-ester.

I claim: 11. A O-alkyl-O-cycloalkyl thiophosphoric acid-S-phenylester ofthe formula R11 R10 0 l in which R stands for a member selected from thegroup consisting of lower alkyl with 1 to 4 carbon atoms and .lowerialkenyl with 1 to 4 canbon atoms,

R stands -for cyclo'alkyl with 5 to 6 canbon atoms,

R stands for a member selected from the group consisting of halogen,lower alkyl with 1 to 4 carbon atoms and lower alkoxy with 1 to 4 carbonatoms, and

It stands for a member selected from the group consisting of -1 and 2.

'2. A compound according to claim 1 wherein R is lower alkyl, R iscyclohexyl, R is halogen and n is 1. 3. A compound according to claim '1wherein R is lower alkyl, R is cyclopentyl, R is halogen and n is 1.

4. O methyl 0 cyclohexyl thiolphosphoric acid- S( p-chlorophenyl -ester.

5. O ethyl O cyclohexyl thiolphosphorie acid- S (pchl orophenyl) -ester.

6. O isopropyl O cyclohexyl thiolphosphoricacid-S(p-chlorophenyl -ester.

7. O methyl O cyclohexyl thiolphosphor-ic acid- S(m-ch1orophenyl)-cster.

8. O ethyl O cyclohexyl thiolphosphoric acid- S'(m-chlorophenyl)-ester.

9. 0 methyl O cyclopentyl thiolphosphoricacid-S(p-chlorop,henyl)-ester.

10. O ethyl O cyclopentyl thiolphosphoric acid- S(p-ohlorophenyl)-ester.

11. O ethyl O cyclohexyl thiolphosphoric acid- S(p-chloro-m-methylphenyl-ester.

12. O ethyl O cyclohexyl thiolphosphoric acid-S(p-clrloro-m-methoxypheny1)-ester.

References Cited by the Examiner UNITED STATES PATENTS 2,690,450 9/54Gilbert et a1 260--461 2,861,876 11/58 Birum 260-461 X 2,962,518 11/60Lorenz ct a1. 26046'1 OTHER REFERENCES Bianchetti: Rend 1st LombardoSci, Pt. I, vol. 91, pp. 68-75 (1957).

CHARLES B. PARKER, Primary Examiner,

1. A O-ALKYL-O-CYCLOALKYL THIOPHOSPHORIC ACID-S-PHENYLESTER OF THEFORMULA